We propose to continue our efforts to characterize the polypeptides and DNA of hepatitis B virus (HBV) and to study its relationship to hepatocellular carcinoma. We have recently discovered a virus with similar ultrastructural, antigenic, molecular and biological features in wild Beechey ground squirrels (ground squirrel hepatitis virus or GSHV) trapped in Northern California. We propose to develop this animal model of infection with a virus similar to HBV and determine the natural history of infections and the associated diseases. We will compare the antigenic and molecular structures of the two viruses and attempt to infect cells in culture with both viruses and the viral DNAs. We will attempt to produce hepatitis B surface antigen (HBsAg) in large quantities in cell culture by introducing the gene for the major HBsAg polypeptide into cells as part of a plasmid vector with SV 40 promotors. HBsAg produced in this way will be tested for immunogenicity and assessed as a potential HBV vaccine. This approach will be used to attempt to identify coding regions in HBV DNA for other viral gene products. Attempts will be made to produce monoclonal human anti-HBs as a potential source for passive immunization against HBV.